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Introduction: Caloric restriction (CR) has been widely shown to have both cardioprotective and neuroprotective properties. However, nearly all studies have investigated chronic CR with mechanisms linked to the upregulation of SIRT-1 and BDNF. Minimal to no focus has been placed on the potential benefits of transient CR in models of brain injury, including stroke. Furthermore, the effects of transient CR in cardiac arrest-induced global cerebral ischemia have not been evaluated. We investigated the effects of overnight (~14-hour) CR on survival and neurological outcome in a rodent model of cardiac arrest (CA). Methods: Adult male Wistar rats (n=28) were divided into 75% CR (n=14) and non-CR (n=14) groups 14hrs prior to rats undergoing intubation, mechanical ventilation, cannulation of femoral vessels, and 8 minutes of asphyxial CA followed by cardiopulmonary resuscitation (CPR). Blood glucose was measured before CA. We conducted neurological deficit scale (NDS) behavioral testing at 4hrs, 24hrs, 48hrs, and 72hrs post-CA. The NDS score ranges from 0 (dead) to 80 (normal). Rats were euthanized after 72hrs and tissue was collected for protein analysis via Western blot. Results: CR, in comparison to no-CR, resulted in significant reduction of mortality (0% vs. 28.6%; Kaplan-Meier log-rank test, p< 0.05). Of those that survived, NDS scores improved significantly in the CR group at 4hrs (32.8±6.1 vs. 24.5±3.3; p Conclusions: Our results demonstrate that ultra-short CR (~14 hours) significantly improves survival and neurological outcome after CA/CPR. Interestingly, these improvements appear to be independent of BDNF or SIRT-1 pathways, commonly linked to chronic CR. While ultra-short CR improved glycemic control in rats, further investigation into the underlying molecular mechanisms are imperative to explore potential translational and therapeutic implications, including for patients at high risk of CA.

Introduction: During cardiac arrest (CA), a major goal of responders is to ascertain the likelihood of successful cardiopulmonary resuscitation (CPR) and optimize efforts accordingly to achieve return of spontaneous circulation (ROSC). Pulseless electrical activity (PEA), a common form of CA in inpatient settings, often allows monitoring of heart rate (HR) immediately preceding cardiopulmonary resuscitation (CPR). We were interested in assessing the role of HR during PEA in outcome of CPR. To evaluate this in a controlled setting, we used a rodent model of asphyxial CA with electrocardiogram (ECG) recordings and neurological testing. We hypothesized that more severe bradycardia may be associated with failure to achieve ROSC and worse neurological outcome if ROSC is achieved. Methods: Adult male Wistar rats (n=25) were anesthetized, intubated, and placed under mechanical ventilation. Needle electrodes were inserted into the rats to obtain continuous ECG data. Rats then underwent 8 minutes of asphyxial CA followed by CPR accompanied with intravenous epinephrine and bicarbonate injections. Neurological deficit scale (NDS) testing was conducted at 24hrs post-ROSC. Results: Of 25 rats that underwent CA, 4 failed to achieve ROSC. HR was measured after 7.5 minutes of asphyxia (i.e. 30 sec. prior to CPR), when the systolic blood pressure was Conclusions: In a rodent asphyxial model of CA mimicking a PEA state, rats failing to achieve ROSC had lower HR immediately prior to CPR. However, in rats achieving ROSC, slower pre-CPR HR is associated with better neurological outcome. These findings appear to be independent of respiratory acidosis. We propose a model and future experimentation that may help define underlying mechanisms. Validation is needed in human studies to assess potential translational implications in a clinical setting.